The Chlamydiae are obligate intracellular parasites of eukaryotic cells which are responsible for endemic sexually transmitted infections and various other disease syndromes. They occupy an exclusive eubacterial phylogenic branch, having no close relationship to any other known organisms. A particular characteristic of the Chlamydiae is their unique life cycle, in which the bacterium alternates between two morphologically distinct forms: an extracellular infective form (elementary bodies, EB) and an intracellular non-infective form (reticulate bodies, RB). The life cycle is completed with the re-organization of RB into EB, which leave the disrupted host cell ready to infect further cells.
Historically, the Clamydiae have been classified in their own order (Chlamydiales) made up of a single family (Chlamydiaceae) which in turn contains a single genus (Chlamydia also referred to as Chlamydophila). More recently, this order has been divided into at least four families including Chlamydia trachomatisceae, ParaChlamydia trachomatisceae, Waddiaceae and Simkaniaceae. In this more recent classification, the Chlamydiaceae family includes genuses of Chlamydophila and Chlamydia trachomatis, Chlamydia trachomatis being a species within the Chlamydia genus. See Ref. 1.
The genome sequences of at least five Chlamydia trachomatis or chlamydophila species are currently known—C. trachomatis, C. pneumoniae, C. muridarum, C. pecorum and C. psittaci (See Refs. 2, 8). The various C. trachomatis strains, of which there are currently at least 18 serovars, may be classified according to their serological reactivities with polyclonal or monoclonal antisera (i.e., “serovars”). These serological differences are typically detected due to differences in the MOMP (Major Outer Membrane Protein) of C. trachomatis. 
The human serovariants (“serovars”) of C. trachomatis are divided into two biovariants (“biovars”). Serovars L1, L2 and L3 are the agents of invasive lymphogranuloma venereum (LGV) which is a sexually transmitted systemic infection. LGV is uncommon in industralised countries but frequent in Africa, Asia, Australian and South America. It predominantly affects lymphatic tissue but may also occur as an acute symptomatic infection without apparent lymph node involvement or tissue reaction at the point of infection. Acute LGV is reported over five times more frequent in men than in women. Other biotypes of C. trachomatis include serovars A, B, Ba, and C which are associated with trachoma, a transmissible condition of the eye.
Serovars A-K (D, E, F, G, H, I, J, and K) are typically associated with genital tract disease. In particular, Serovars D, E, F, H and K account for nearly 85% of genital tract infections (see for example, WO 02/065129) Serovars A-K elicit epithelial infections primarily in the ocular tissue (A-C) or urogenital tract (D-K). Research to date also indicates that the 4 Serovars (or serotypes) responsible for Sexually Transmitted Infections or Diseases (STIs or STDs) in the US and Europe are D-K, preferably D, E, F and I.
More than 4 million new cases of Chlamydia sexually transmitted infections are diagnosed each year in the United States alone (8) and the cost of their treatment has been estimated in 4 billion dollars annually, with 80% attributed to infection and disease of women (9).
Although Chlamydia infection itself causes disease, it is thought that the severity of symptoms in some, patients is actually due to an aberrant or an altered host immune response which may arise from either (i) the nature of the invading Chlamydia organism which may vary from serovar to serovar or (ii) the nature of the subject invaded (for example, the nature of the patient profile). The failure to clear the infection results in persistent immune stimulation and, rather than helping the most, this results in chronic infection with severe consequences, including sterility and blindness. See, e.g., Ref. 9. In addition, the protection conferred by natural Chlamydial infection is usually incomplete, transient, and strain-specific.
Although Chlamydia infections can be treated with several antibiotics, a majority of the female infections are asymptomatic, and antimicrobial therapy may be delayed or inadequate to prevent long term sequelae, expecially in countries with poor hygienic conditions. Multiple-antibiotic-resistant strains of Chlamydia have also been reported (Somani, et al., 2000). Furthermore it has been suggested that antibiotic treatment could lead to the formation of aberrant or altered forms of C. trachomatis that may be reactivated later on (Hammerschlag M. R. 2002. The intracellular life of Chlamydia trachomatis Semin. Pediatr. Infect. Dis. 13:239-248).
Unfortunately the major determinants of Chlamydia pathogenesis are complicated and at present still unclear, mostly due to the intrinsic difficulty in working with this pathogen and the lack of adequate methods for its genetic manipulation. In particular very little is known about the antigenic composition of elementary body surface, that is an essential compartment in pathogen-host interactions, and likely to carry antigens able to elicit a protective immune response.
Due to the serious nature of the disease, there is a desire to provide suitable immunogenic compositions, such as vaccines to deal with an aberrant or altered host cell immune response which may result from, for example, allelic variation in the invading Chlamydia strain and/or aberrant or altered forms of Chlamydia invading strain. These immunogenic compositions may be useful (a) for immunisation against Chlamydial infection or against Chlamydia-induced disease (prophylactic vaccination) or (b) for the eradication of an established chronic Chlamydia infection (therapeutic vaccination). Being an intracellular parasite, however, the bacterium can generally evade antibody-mediated immune responses.
Various antigenic proteins have been described for C. trachomatis, and, the cell surface in particular has been the target of detailed research. See, e.g., Ref. 10. These include, for instance, Pgp3 (Refs. 11, 12, and 13), MOMP (Ref. 14), Hsp60 (GroEL) (Ref. 15) and Hsp70 (DnaK-like) (Ref. 16). Not all of these have proved to be effective vaccines, however, and further candidates have been identified. See Ref. 17.
Vaccines against pathogens such as hepatitis B virus, diphtheria and tetanus typically contain a single protein antigen (e.g. the HBV surface antigen, or a tetanus toxoid). In contrast, acellular whooping cough vaccines typically have at least three B. pertussis proteins, and the Prevnar™ pneumococcal vaccine contains seven separate conjugated saccharide antigens. Other vaccines such as cellular pertussis vaccines, the measles vaccine, the inactivated polio vaccine (IPV) and meningococcal OMV vaccines are by their very nature complex mixtures of a large number of antigens. Whether protection can be elicited by a single antigen, a small number of defined antigens, or a complex mixture of undefined antigens, therefore depends on the pathogen in question.
It is an object of the invention to provide further and improved immunogenic compositions for providing immunity against Chlamydial disease and/or infection. In particular, it is an object of the invention to provide improved immunogenic compositions for providing immunity against aberrant or altered Chlamydia serovar strains (eg strains such as allelic variant strains).
The immunogenic compositions of the present invention are based on a combination of one or more (e.g. two or more) C. trachomatis antigens. The immunogenic compositions may include one or more of the same Chlamydia trachomatis antigens from different Chlamydia trachomatis serovars and/or one of more of the same or different Chlamydia trachomatis antigen from the different Chlamydia trachomatis serovars.